A novel role for the SUMO E3 ligase PIAS1 in cancer metastasis
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https://doi.org/10.18632/oncoscience.27
Shorafidinkhuja Dadakhujaev1,2, Carolina Salazar-Arcila1,3, Stuart J. Netherton1,2, Amrita Singh Chandhoke1,2, Arvind Kumar Singla1,3, Frank R. Jirik1,3, Shirin Bonni1,2
1 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada
2 Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada
3 McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada
Correspondence:
Shirin Bonni, email:
Keywords: Cancer metastasis, SUMO E3 ligase, PIAS1, three-dimensional cultures
Received: February 17, 2014 Accepted: March 31, 2014 Published: March 31, 2014
Abstract
Tumor metastasis contributes to the grave morbidity and mortality of cancer, but the mechanisms underlying tumor cell invasiveness and metastasis remain incompletely understood. Here, we report that expression of the SUMO E3 ligase PIAS1 suppresses TGFβ-induced activation of the matrix metalloproteinase MMP2 in human breast cancer cells. We also find that knockdown of endogenous PIAS1 or inhibition of its SUMO E3 ligase activity stimulates the ability of TGFβ to induce an aggressive phenotype in three-dimensional breast cancer cell organoids. Importantly, inhibition of the SUMO E3-ligase activity of PIAS1 in breast cancer cells promotes metastases in mice in vivo. Collectively, our findings define a novel and critical role for the SUMO E3 ligase PIAS1 in the regulation of the invasive and metastatic potential of malignant breast cancer cells. These findings advance our understanding of cancer invasiveness and metastasis with potential implications for the development of biomarkers and therapies in breast cancer.
